TEL AVIV, Israel—Crohn’s disease, a devastating chronic gastrointestinal disorder with an unknown cause and no cure, is characterized by abdominal pain, diarrhea, bleeding, bowel obstruction and numerous other systemic symptoms. It affects about 1.5 million people globally and creates an economic burden of more than $6 billion annually in the U.S. Alone.

Currently, Crohn’s disease is treated with anti-inflammatories, immunosuppressants and biologics that address autoimmune disorders. These therapies, which treat inflammation associated with Crohn’s, are not curative. They are only effective in some patients, and even then, only for a limited time. These medications are also associated with side effects, including serious infections and malignancy. There is a clear unmet medical need for additional treatment options for Crohn’s patients.

RedHill Biopharma Ltd., which just announced encouraging results in Phase 3 studies, became involved in the development of RHB-104 in 2010 when it acquired the rights to the drug combination that had been developed by Prof. Thomas Borody, an Australian gastroenterologist. RHB-104 was originally developed based on the hypothesis that Crohn’s disease is triggered by an infection in susceptible patients.

Borody’s research into an infection/inflammation cause of Crohn’s disease pointed towards Mycobacterium avium subspecies Paratuberculosis (MAP) as the likely culprit. He developed a combination therapy of three antibiotics specifically directed against MAP, which eventually evolved into RHB-104.

Initially, Borody conducted a few small studies with the combination, after which Pharmacia/Pfizer then conducted a large study in Australia. While it missed its primary endpoint, the study showed promising remission results during a subsequent re-analysis of the trial data. RedHill took over the program in 2010, with Borody as its consultant, reformulated the combination into RHB-104 (all-in-one capsule) and completed the now successful Phase 3 MAP US study, the first global, double-blind, placebo-controlled study to demonstrate the efficacy of anti-MAP therapy in Crohn’s disease. This study met its primary endpoint of remission at week 26 (37 percent vs. 23 percent with p-value =0.013) as well as key secondary endpoints, including early remission at week 16 (42 percent vs. percent with p-value =0.019) and durable remission at weeks 16 through 52 (18 percent vs. 9 percent with p-value =0.038), demonstrating an improvement of 100 percent over placebo.

Dror Ben-Asher, RedHill’s CEO, said that, “The compelling top-line results with RHB-104, our potential groundbreaking therapy, are a remarkable accomplishment. We look forward to discussing the path to approval with the FDA and to accelerating discussions with potential pharma partners.” Worldwide sales of Crohn’s disease therapies are estimated to exceed $10 billion in 2018.

RHB-104 is a combination of three antibiotics—clarithromycin, clofazimine and rifabutin—in a single oral capsule with potent intracellular, anti-mycobacterial and anti-inflammatory properties. The positive top-line results in the MAP US study demonstrate that RHB-104 provides a significant clinical benefit to Crohn’s patients and could be a highly promising and much-needed treatment option for Crohn’s patients.

The recently reported MAP US study demonstrated a statistically and clinically meaningful benefit to Crohn’s patients (which is on par or compares favorably with leading standard-of-care treatments). Of note, the Crohn’s patients in the study were on a variety of standard approved therapies but remained ill nonetheless. Furthermore, this significant benefit to Crohn’s patients is obtained with an excellent safety and tolerability profile that does not expose the patient to some of the more serious side effects of biologics. These results and the product profile make RHB-104 a highly promising potential addition for the treatment of Crohn’s disease. RHB-104 could be positioned as both a first-line therapeutic option and also as a complementary treatment option together with leading standard of care therapies.

“RHB-104 could lead to a paradigm shift in the treatment of Crohn’s disease, a chronic and debilitating—and currently incurable—condition with a strong unmet medical need,” commented Dr. David Graham, lead investigator of the RHB-104 MAP US Phase 3 study. “Many patients with Crohn’s disease do not achieve remission on current standard-of-care therapies, which are accompanied with poor side effects. RHB-104 appears to have the potential to become a promising, new, orally administered therapy for this important debilitating disease.”

He added that, “We plan to complete analysis of the data from our MAP US study (including MAP status, mucosal healing, sub-populations analysis and pharmacokinetics) over the coming months and consult with key opinion leaders. We will then present the data package to FDA and discuss the development path to potential approval of RHB-104. Additional clinical studies will likely be required to support a New Drug Application for RHB-104.”